A 5-day-old neonate is identified on newborn screen with elevated 17-hydroxyprogesterone. She presents with vomiting, poor feeding, weight loss, hypoglycemia, hyponatremia (Na 125 mEq/L), and hyperkalemia (K 6.8 mEq/L). Which enzyme deficiency is most likely?

• A 21-hydroxylase deficiency ✓
• B 11-beta hydroxylase deficiency
• C 3-beta hydroxysteroid dehydrogenase deficiency
• D 17-alpha hydroxylase deficiency

Explanation

21-hydroxylase (CYP21A2) deficiency accounts for >95% of congenital adrenal hyperplasia (CAH) cases. The classic salt-wasting form presents in the neonatal period with adrenal crisis: hyponatremia, hyperkalemia, hypoglycemia, shock, and vomiting. Elevated 17-hydroxyprogesterone (precursor accumulation) is the biochemical hallmark and the basis of newborn screening. The 21-hydroxylase enzyme is required for both cortisol and aldosterone synthesis; its deficiency causes cortisol deficiency (ACTH excess, androgen overproduction) and mineralocorticoid deficiency (salt wasting). Treatment is hydrocortisone (for glucocorticoid replacement) and fludrocortisone (for mineralocorticoid replacement).

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.